The prefrontal cortex (PFC) plays an important role in executive function and has been implicated in sensory working memory and attention. The cognitive dysfunctions found in schizophrenia and other mental disorders has been linked to the dysfunction of PFC, and thus, understanding the functional circuitry that mediates cognitive function in PFC is of major relevance to the study of mental illness. In spite of the evidence that the influence of PFC on sensory cortex is important for cognitive function, the nature of this influence is still poorly understood. To understand such influences it is important to determine how PFC represents signals it receives from sensory neurons. To examine this problem we chose tasks involving visual motion since its neural code and motion processing cortical areas have been examined in some detail. Our goal is to characterize the representation of visual motion in the PFC and to examine the top-down influences it provides to motion processing area MT. During the past grant period we showed that at the fovea the majority of the PFC neurons show direction selective (DS) responses, suggesting their MT origins. We also characterized the circuitry involved in assigning task relevance to such stimuli and characterized in detail memory-related signals its neurons carry. We now examine whether the representation of motion in the PFC across space reflects the local nature of the bottom-up motion signals arriving from MTs in both hemispheres (Aim #1). This information has important implications for the way the PFC interprets sensory signals appearing in different portions of the visual field and for its top-down influences on the highly retinotopic and stimulus selective MT neurons. We will use reversible inactivation of the PFC to determine its influence on activity of MT neurons during all components of memory for motion tasks (Aim #2) and its contribution to behavioral performance of these tasks (Aim #3). We will record spiking activity and local field potentials as measure motion thresholds while monkeys compare directions or speeds of two sequential moving stimuli presented within and between contralateral and ipsilateral hemifields. These studies will provide new information about the way PFC represents and controls sensory signals used during working memory tasks. The results will have important implications for elucidating the basis of cognitive dysfunction in schizophrenia, long associated with deficits in sensory working memory and impaired prefrontal function. PUBLIC HEALTH RELEVANCE: Many everyday tasks, like crossing the street, involve processing and comparing visual motion appearing in different locations at different times. Such tasks require processes termed working memory that depend on normally functioning prefrontal cortex. This research seeks to understand the fundamental mechanisms by which prefrontal cortex allows us to perform such tasks. The results will have important implications for elucidating the basis of cognitive disorders of schizophrenia, shown to have impaired prefrontal function and deficits in working memory.